Involvement of Type 10 17β-Hydroxysteroid Dehydrogenase in the Pathogenesis of Infantile Neurodegeneration and Alzheimer’s Disease
Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the <i>HSD17B10</i> gene product playing an appreciable role in cognitive functions. It is the main hub of exercise-upregulated mitochondrial proteins and is involved in a variety of metabolic pathways including neurosteroid metabol...
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/24/17604 |
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| author | Xue-Ying He Jannusz Frackowiak Carl Dobkin William Ted Brown Song-Yu Yang |
| author_facet | Xue-Ying He Jannusz Frackowiak Carl Dobkin William Ted Brown Song-Yu Yang |
| author_sort | Xue-Ying He |
| collection | DOAJ |
| description | Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the <i>HSD17B10</i> gene product playing an appreciable role in cognitive functions. It is the main hub of exercise-upregulated mitochondrial proteins and is involved in a variety of metabolic pathways including neurosteroid metabolism to regulate allopregnanolone homeostasis. Deacetylation of 17β-HSD10 by sirtuins helps regulate its catalytic activities. 17β-HSD10 may also play a critical role in the control of mitochondrial structure, morphology and dynamics by acting as a member of the Parkin/PINK1 pathway, and by binding to cyclophilin D to open mitochondrial permeability pore. 17β-HSD10 also serves as a component of RNase P necessary for mitochondrial tRNA maturation. This dehydrogenase can bind with the Aβ peptide thereby enhancing neurotoxicity to brain cells. Even in the absence of Aβ, its quantitative and qualitative variations can result in neurodegeneration. Since elevated levels of 17β-HSD10 were found in brain cells of Alzheimer’s disease (AD) patients and mouse AD models, it is considered to be a key factor in AD pathogenesis. Since data underlying Aβ-binding-alcohol dehydrogenase (ABAD) were not secured from reported experiments, ABAD appears to be a fabricated alternative term for the <i>HSD17B10</i> gene product. Results of this study would encourage researchers to solve the question why elevated levels of 17β-HSD10 are present in brains of AD patients and mouse AD models. Searching specific inhibitors of 17β-HSD10 may find candidates to reduce senile neurodegeneration and open new approaches for the treatment of AD. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T20:40:53Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7ee8e962f34642498be956e65173c3122023-12-22T14:15:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124241760410.3390/ijms242417604Involvement of Type 10 17β-Hydroxysteroid Dehydrogenase in the Pathogenesis of Infantile Neurodegeneration and Alzheimer’s DiseaseXue-Ying He0Jannusz Frackowiak1Carl Dobkin2William Ted Brown3Song-Yu Yang4Department of Molecular Biology, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USADepartment of Developmental Neurobiology, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USADepartment of Human Genetics, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USADepartment of Human Genetics, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USADepartment of Molecular Biology, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USAType 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the <i>HSD17B10</i> gene product playing an appreciable role in cognitive functions. It is the main hub of exercise-upregulated mitochondrial proteins and is involved in a variety of metabolic pathways including neurosteroid metabolism to regulate allopregnanolone homeostasis. Deacetylation of 17β-HSD10 by sirtuins helps regulate its catalytic activities. 17β-HSD10 may also play a critical role in the control of mitochondrial structure, morphology and dynamics by acting as a member of the Parkin/PINK1 pathway, and by binding to cyclophilin D to open mitochondrial permeability pore. 17β-HSD10 also serves as a component of RNase P necessary for mitochondrial tRNA maturation. This dehydrogenase can bind with the Aβ peptide thereby enhancing neurotoxicity to brain cells. Even in the absence of Aβ, its quantitative and qualitative variations can result in neurodegeneration. Since elevated levels of 17β-HSD10 were found in brain cells of Alzheimer’s disease (AD) patients and mouse AD models, it is considered to be a key factor in AD pathogenesis. Since data underlying Aβ-binding-alcohol dehydrogenase (ABAD) were not secured from reported experiments, ABAD appears to be a fabricated alternative term for the <i>HSD17B10</i> gene product. Results of this study would encourage researchers to solve the question why elevated levels of 17β-HSD10 are present in brains of AD patients and mouse AD models. Searching specific inhibitors of 17β-HSD10 may find candidates to reduce senile neurodegeneration and open new approaches for the treatment of AD.https://www.mdpi.com/1422-0067/24/24/17604ABADAlzheimer’s disease17β-HSD10mitochondriamultifunctional proteinneurosteroid metabolism |
| spellingShingle | Xue-Ying He Jannusz Frackowiak Carl Dobkin William Ted Brown Song-Yu Yang Involvement of Type 10 17β-Hydroxysteroid Dehydrogenase in the Pathogenesis of Infantile Neurodegeneration and Alzheimer’s Disease International Journal of Molecular Sciences ABAD Alzheimer’s disease 17β-HSD10 mitochondria multifunctional protein neurosteroid metabolism |
| title | Involvement of Type 10 17β-Hydroxysteroid Dehydrogenase in the Pathogenesis of Infantile Neurodegeneration and Alzheimer’s Disease |
| title_full | Involvement of Type 10 17β-Hydroxysteroid Dehydrogenase in the Pathogenesis of Infantile Neurodegeneration and Alzheimer’s Disease |
| title_fullStr | Involvement of Type 10 17β-Hydroxysteroid Dehydrogenase in the Pathogenesis of Infantile Neurodegeneration and Alzheimer’s Disease |
| title_full_unstemmed | Involvement of Type 10 17β-Hydroxysteroid Dehydrogenase in the Pathogenesis of Infantile Neurodegeneration and Alzheimer’s Disease |
| title_short | Involvement of Type 10 17β-Hydroxysteroid Dehydrogenase in the Pathogenesis of Infantile Neurodegeneration and Alzheimer’s Disease |
| title_sort | involvement of type 10 17β hydroxysteroid dehydrogenase in the pathogenesis of infantile neurodegeneration and alzheimer s disease |
| topic | ABAD Alzheimer’s disease 17β-HSD10 mitochondria multifunctional protein neurosteroid metabolism |
| url | https://www.mdpi.com/1422-0067/24/24/17604 |
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